rs2740351

Positions:

• chr17-740186-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024792.3(TLCD3A):​c.409-319G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,126 control chromosomes in the GnomAD database, including 34,118 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (34118 hom., cov: 33)
• Consequence: TLCD3A NM_024792.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267

Genes affected

TLCD3A (HGNC:29646): (TLC domain containing 3A) The protein encoded by this gene is a membrane-associated protein that promotes lung carcinogenesis. The encoded protein may be involved in amino acid transport and glutathione metabolism since it can interact with a solute carrier family member (SLC3A2) and an isoform of gamma-glutamyltranspeptidase-like 3. An alternatively spliced variant encoding a protein that lacks a 32 aa internal segment showed the opposite effect, inhibiting lung cancer cell growth. Knockdown of this gene also inhibited lung carcinogenesis and tumor cell growth. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLCD3A	NM_024792.3	c.409-319G>A		intron_variant		ENST00000308278.13	NP_079068.1
TLCD3A	NM_001318006.2	c.409-1115G>A		intron_variant			NP_001304935.1
TLCD3A	NM_001318007.2	c.207-319G>A		intron_variant			NP_001304936.1
TLCD3A	NM_001318008.2	c.207-1115G>A		intron_variant			NP_001304937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLCD3A	ENST00000308278.13	c.409-319G>A		intron_variant		1	NM_024792.3	ENSP00000312017	P1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 100095 AN: 152008 Hom.: 34064 Cov.: 33

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.658

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.659 AC: 100208 AN: 152126 Hom.: 34118 Cov.: 33 AF XY: 0.661 AC XY: 49123 AN XY: 74366

Gnomad4 AFR AF: 0.834

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.661

Alfa AF: 0.585 Hom.: 42052

Bravo AF: 0.673

Asia WGS AF: 0.694 AC: 2408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.1
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2740351; hg19: chr17-643426; COSMIC: COSV56747366; COSMIC: COSV56747366;